4-(4-Fluorophenyl)-7-((4-formyl-1H-pyrazol-1-yl)methyl)quinoline-2-carboxamide → 7-({4-[Cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide

HRID 922765Notes

Reaction equation

HRID 922765 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([CH2:18][N:19]4[CH:23]=[C:22]([CH:24]=[O:25])[CH:21]=[N:20]4)=[CH:15][CH:16]=3)[N:11]=[C:10]([C:26]([NH2:28])=[O:27])[CH:9]=2)=[CH:4][CH:3]=1.[CH:29]1([Mg]Br)[CH2:31][CH2:30]1>C1COCC1>[CH:29]1([CH:24]([OH:25])[C:22]2[CH:21]=[N:20][N:19]([CH2:18][C:14]3[CH:13]=[C:12]4[C:17]([C:8]([C:5]5[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=5)=[CH:9][C:10]([C:26]([NH2:28])=[O:27])=[N:11]4)=[CH:16][CH:15]=3)[CH:23]=2)[CH2:31][CH2:30]1

Participants

4

Reactant 2

HCID 895451674-(4-Fluorophenyl)-7-((4-formyl-1H-pyrazol-1-yl)methyl)quinoline-2-carboxamideHCID 178418630HCID 178418630, compound

Product 1

HCID 715657377-({4-[Cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamideYield 62.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 4-(4-fluorophenyl)-7-[(4-formyl-1H-pyrazol-1-yl)methyl]quinoline-2-carboxamide (3-9, 36.0 mg, 0.0960 mmol, 1.0 equiv.) in anhydrous THF, under nitrogen was added dropwise 0.5 M cyclopropylmagnesium bromide in THF (0.769 mL, 0.385 mmol, 4.0 equiv.). The resulting mixture was stirred at 0° C. for 1 hour, quenched with sat. aqueous NH4Cl, extracted with ethyl acetate (3×5.0 mL), dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier) to afford 7-({4-[cyclopropyl(hydroxy)methyl]-1H-pyrazol-1-yl}methyl)-4-(4-fluorophenyl)quinoline-2-carboxamide (3-10, 25.0 mg, 62.4%) as a colorless solid. 1H NMR (400 MHz, CDCl3): δ 8.228 (s, 1H); 8.084 (br s, 1H); 7.995 (s, 1H); 7.929 (d, J=8.81 Hz, 1H); 7.625 (s, 1 μl); 7.515 (s, 1H); 7.442-7.506 (m, 3H); 7.206-7.249 (m, 2H); 5.777 (br s, 1 μl); 5.526 (s, 2H); 4.044 (d, J=8.48 Hz, 1H); 1.185-1.258 (m, 1H); 0.599-0.638 (m, 2H); 0.331-0.454 (m, 2H). LRMS m/z (M+H)+ 417.2 found, 417.2 required.

Workup

  1. customquenched with sat. aqueous NH4Cl
  2. extractionextracted with ethyl acetate (3×5.0 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase HPLC (H2O/CH3CN gradient w/0.1% TFA modifier)

Sources & evidence

ORD record
ord-f31625cebc23491b8315621deb88d1ff
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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